Virus infection can lead to many diseases which are severely harmful to the health and life of the human being. Today, more than 3000 species of viruses over the whole world have been discovered and new types of viruses are being found. According to statistics, 60%-65% epidemic infectious diseases are caused by virus infection. Because of complexity of reciprocal action between viruses and hosts, most of antiviral agents, when exerting therapeutic action, have side-effects on the human being or have lower antiviral function. This is the main reason why the antiviral drugs are developed so slowly. As for the types of existing antiviral drugs, the antiviral drugs now used in clinic are still very scarce and are far from meeting the need of preventing and curing the virus diseases. It is important to investigate new antiviral drugs which have new antiviral mechanism, potent inhibitory activity and low toxicity.
5-hydroxyindole-3-carboxylate derivatives were originally studied as a new type of anti-influenza virus drug. The literatures, such as Grinev A. H., et al. Khim-Farm Zh, 1987, 21(1), 52; Parisheva E. K. et al. Khim Farm Zh, 1988, 22(5), 565; Mezentseva M. V. et al. Khim Farm Zh, 1990, 24(10), 52; Otova S. A., et al. Khim Farm Zh, 1992, 26(1), 52; Zotova S. A. et al. Khim Farm Zh, 1995, 29(1), 51, reported the synthesis of some 5-hydroxyindole-3-carboxylate derivatives and their pharmacological activity. The experimental results show that some of them had anti-influenza virus activity and interferon-inducing and immunostimulative functions.
Ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenyl-thiomethyl)-1H-indole-3-carboxylate hydrochloride monohydrate (Arbidol, PCT Int Appl. WO 9008135(RUSS), 1990-6-26), one of 5-hydroxyindole-3-carboxylates, was launched in Russia Federation by VNIKhFI Co. Ltd. in 1993 for the prophylaxis and treatment of influenza A and B and acute respiratory viral infections.
In order to develop new type of highly effective antiviral drugs, the inventor has performed extensive studies on 5-hydroxy-indole-3-carboxylate derivatives. Modifications and changes are made on several structural sites and a new series of 5-hydroxyindole-3-carboxylate derivatives are synthesized. Their antiviral activities are determined in vitro and the results showed that they had anti-influenza virus activity. Surprisingly, they are found to have potent anti-HBV and anti-HIV activities. So the compounds are studied intensively and the invention is thereby completed.